Permethrin induced cytotoxicity of rat splenocytes: Protective effect of N-acetylcysteine

Abstract

The present study was designed to determine the molecular mechanism associated with permethrin induce cytotoxicity. Rat splenocytes were incubated with increasing concentration of permethrin (0-39 ug/ml) for 6 to 24 h. Cytotoxic effect of permethrin was evaluated by MTT assay. To assess the underneath mechanism of cytotoxicity, different biochemical indices of cell death namely Annexin V binding assay, DNA fragmentation, and levels of caspase 3 were analyzed. To evaluate the oxidative stress, glutathione depletion and melondialdehyde levels were analyzed. MTT assay revealed that permethrin induces cytotoxicity in dose-dependent way. In Annexin-V binding assay, above 7.8 µg/ml concentration, significant necrosis of cells was noticed and consistent with DNA fragmentation assay. A significant dose and time dependent depletion of cellular glutathione (GSH) and increased MDA levels were observed and consistent with the percentage of cells undergoing apoptosis. Co administration of N-acetycysteine mitigates permethrin- induced apoptosis, showing the role of oxidative stress in apoptosis induction. The present study gives experimental evidence that emphasizing the role of oxidative stress in permethrin-induced cytotoxicity in rat splenocytes in vitro.